A Randomized Trial of Levodopa as Treatment for Residual Amblyopia (ATS 17)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 139
- 试验地点
- 1
- 主要终点
- Distribution of Amblyopic Eye Visual Acuity Change From Baseline
研究概览
简要总结
The purpose of this study is to evaluate the efficacy and safety of oral levodopa and patching versus oral placebo and patching as treatment for residual amblyopia in children 7 to <13 years old with visual acuity of 20/50 to 20/400 in the amblyopic eye.
详细描述
Amblyopia is the most common cause of monocular visual impairment in both children and young and middle-aged adults. Both patching and atropine are accepted treatment modalities for the management of moderate amblyopia in children. Despite best efforts with conventional amblyopia treatment, many older children and teenagers with amblyopia fail to achieve normal visual acuity in the amblyopic eye. In a previous PEDIG study where children 7 to 12 years old were treated with atropine and patching, only 36% of the children with moderate amblyopia and only 23% of the children with severe amblyopia achieved 20/40 or better acuity.
Many clinicians have recognized that conventional therapies with patching and atropine have not been universally successful and have sought alternatives. PEDIG has discussed for several years the problem of residual amblyopia and how the remaining visual acuity deficit could be reduced. A number of research groups have evaluated the short term use of oral levodopa-carbidopa as an adjunct to patching therapy for older children.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 7 Years 至 12 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 7 to 12
- •Amblyopia associated with strabismus, anisometropia, or both
- •Criteria for strabismus: One of the following criteria must be met: Heterotropia at distance and/or near fixation on examination (with or without spectacles); History of strabismus surgery; Documented history of strabismus which is no longer present (which in the judgment of the investigator could have caused amblyopia)
- •Criteria for anisometropia: One of the following criteria must be met: ≥0.50 D difference between eyes in spherical equivalent; ≥1.50 D difference between eyes in astigmatism in any meridian
- •Visual acuity, measured in each eye (amblyopic eye without cycloplegia) within 7 days prior to enrollment using the E-ETDRS protocol by a study certified visual acuity tester as follows:
- •Visual acuity in the amblyopic eye 18 to 67 letters inclusive (20/50 to 20/400)
- •Visual acuity in the fellow eye ≥78 letters (20/25 or better)
- •Current amblyopia treatment (other than spectacles)
- •12 weeks of at least 2 hours of occlusion per day prescribed for the fellow eye during the immediate pre-enrollment period.
- •While on current treatment, visual acuity has not improved one line (5 letters) or more since a non-study visit at least 6 weeks ago. Both acuity measurements to define no improvement must have been done using the same testing method.
- •Treatment with atropine at any time during this pre-enrollment period is not allowed.
- •Any treatment prior to the current patching episode with stable acuity is acceptable.
- •Spectacle correction (if applicable) for measurement of enrollment visual acuity must meet the following criteria and be based on a cycloplegic refraction that is no more than 6 months old:
- •Requirements for spectacle correction:
- •Spherical equivalent must be within 0.50 D of fully correcting the anisometropia.
- •Hypermetropia of 3.00D or more must be corrected.
- •Hypermetropia must not be under corrected by more than 1.50 D spherical equivalent, and reduction in plus sphere must be symmetric in the two eyes.
- •Cylinder power in both eyes must be within 0.50 D of fully correcting the astigmatism.
- •Cylinder axis in both eyes is within 6 degrees of the axis in the spectacles when cylinder power is ≥1.00 D.
- •Myopia of amblyopic eye greater than 0.50 D by spherical equivalent must be corrected, and the glasses must not under correct the myopia by more than 0.25 D or overcorrect it by more than 0.50 D.
- •Spectacles meeting above criteria must be worn :until visual acuity in amblyopic eye is stable (defined as 2 consecutive visual acuity measurements by the same testing method at least 4 weeks apart with no improvement of one line (5 letters) or more.
- •Eye examination within 6 months prior to enrollment
- •Parent available for at least one year of follow-up, has access to phone), and willing to be contacted by clinical site and Jaeb Center staff
- •In the investigator's judgment, the subject is likely to comply with prescribed treatment (e.g., no history of poor compliance with patching treatment) and unlikely to continue to improve by using 2 hours of patching per day alone.
排除标准
- •Myopia more than -6.00 D (spherical equivalent) in either eye.
- •Current vision therapy or orthoptics
- •Ocular cause for reduced visual acuity
- •nystagmus per se does not exclude the subject if the above visual acuity criteria are met
- •Prior intraocular or refractive surgery
- •History of narrow-angle glaucoma
- •Bronchial asthma or severe pulmonary disease
- •Strabismus surgery planned within 26 weeks
- •Known allergy to levodopa or carbidopa
- •History of dystonic reactions
- •Current use of oral iron supplements including multivitamins containing iron during treatment with levodopa-carbidopa
- •Current use of antihypertensive, anti-depressant medications, phenothiazines, butyrophenones, risperidone and isoniazid, non-specific monoamine oxidase inhibitors, or medication for the treatment of attention deficit hyperactivity disorder
- •Known liver disease
- •History of melanoma
- •Known psychological problems
- •Known skin reactions to patch or bandage adhesives
- •Prior levodopa treatment
- •Treatment with topical ophthalmic atropine within the past 12 weeks
- •A physician-prescribed diet high in protein
- •Females who are pregnant, lactating, or intend to become pregnant within the next 34 weeks.
- •A negative urine pregnancy test will be required for all females who have experienced menarche.
- •Requirements regarding pregnancy testing prior to enrollment may be further defined by each individual Institutional Review Board.
研究组 & 干预措施
Levodopa/Carbidopa
Levodopa 0.76 mg/kg with Carbidopa 0.17 mg/kg tid
干预措施: Levodopa/Carbidopa (Drug)
Levodopa/Carbidopa
Levodopa 0.76 mg/kg with Carbidopa 0.17 mg/kg tid
干预措施: Patching (Other)
Placebo
Oral placebo tid
干预措施: Placebo (Drug)
Placebo
Oral placebo tid
干预措施: Patching (Other)
结局指标
主要结局
Distribution of Amblyopic Eye Visual Acuity Change From Baseline
时间窗: 18 weeks after enrollment
The primary outcome is the amblyopic eye visual acuity letter score measured at the 18-week primary outcome visit following a rapid taper of study medicine beginning at week 16. The primary analytic approach will be a treatment group comparison of the mean amblyopic eye visual acuity adjusted for baseline acuity. Visual acuity was measured in each eye (right eye first) by a study-certified VA tester using the Electronic Early Treatment of Diabetic Retinopathy Study (E-ETDRS©) visual acuity protocol. Five letters is equivalent to one logMAR line.
Mean Amblyopic Eye Visual Acuity Change From Baseline
时间窗: 18 weeks after enrollment
The primary outcome is the amblyopic eye visual acuity letter score measured at the 18-week primary outcome visit following a rapid taper of study medicine beginning at week 16. The primary analytic approach will be a treatment group comparison of the mean amblyopic eye visual acuity adjusted for baseline acuity. Visual acuity was measured in each eye (right eye first) by a study-certified VA tester using the Electronic Early Treatment of Diabetic Retinopathy Study (E-ETDRS©) visual acuity protocol. Five letters is equivalent to one logMAR line.
次要结局
- Amblyopic Eye Visual Acuity Improvement Treatment Group Comparison at 18 Weeks(18 weeks after enrollment)
- Distribution of Amblyopic Eye Visual Acuity at 18 Weeks(18 weeks after enrollment)
- Mean Amblyopic Eye Visual Acuity at 18 Weeks(18 weeks after enrollment)
- Amblyopic Eye Visual Acuity Improvement Treatment Group Comparison at 4 Weeks(4 weeks after enrollment)
- Amblyopic Eye Visual Acuity Improvement Treatment Group Comparison at 10 Weeks(10 weeks after enrollment)
- Amblyopic Eye Visual Acuity Improvement Treatment Group Comparison at 16 Weeks(16 weeks after enrollment)
- Amblyopic Eye Visual Acuity Improvement Treatment Group Comparison at 26 Weeks(26 weeks after enrollment)
- Amblyopia Resolutionat 4 Weeks(4 weeks after enrollment)
- Amblyopia Resolution at 10 Weeks(10 weeks after enrollment)
- Mean Fellow Eye Visual Acuity Change From Baseline at 18 Weeks(18 weeks after enrollment)
- Amblyopia Resolution at 16 Weeks(16 weeks after enrollment)
- Amblyopia Resolution at 18 Weeks(18 weeks after enrollment)
- Amblyopia Resolution at 26 Weeks(26 weeks after enrollment)
- Distribution of Amblyopic Eye Visual Acuity Change From Baseline at 4 Weeks(4 weeks after enrollment)
- Mean Change in Amblyopic Eye Visual Acuity From Baseline at 4 Weeks(4 weeks after enrollment)
- Distribution of Amblyopic Eye Visual Acuity Change From Baseline at 10 Weeks(10 weeks after enrollment)
- Mean Change in Amblyopic Eye Visual Acuity From Baseline at 10 Weeks(10 weeks after enrollment)
- Distribution of Amblyopic Eye Visual Acuity Change From Baseline at 16 Weeks(16 weeks after enrollment)
- Mean Change in Amblyopic Eye Visual Acuity From Baseline at 16 Weeks(16 weeks after enrollment)
- Distribution of Amblyopic Eye Visual Acuity Change From Baseline at 26 Weeks(26 weeks after enrollment)
- Mean Change in Amblyopic Eye Visual Acuity From Baseline at 26 Weeks(26 weeks after enrollment)
- Distribution of Fellow Eye Visual Acuity at 18 Weeks(18 weeks after enrollment)
- Mean Fellow Eye Visual Acuity at 18 Weeks(18 weeks after enrollment)
- Distribution of Fellow Eye Visual Acuity Change From Baseline at 18 Weeks(18 weeks after enrollment)
- Mean Child Symptom Survey Score at Enrollment(At enrollment)
- Mean Child Symptom Survey Score at 4 Weeks(4 weeks after enrollment)
- Mean Child Symptom Survey Score at 10 Weeks(10 weeks after enrollment)
- Mean Child Symptom Survey Score at 16 Weeks(16 weeks after enrollment)
- Mean Child Symptom Survey Score at 18 Weeks(18 weeks after enrollment)
- Mean Child Symptom Survey Score at 26 Weeks(26 weeks after enrollment)
- Mean Parent Symptom Survey Score at Enrollment(At enrollment)
- Mean Parent Symptom Survey Score at 4 Weeks(4 weeks after enrollment)
- Mean Parent Symptom Survey Score at 26 Weeks(26 weeks after enrollment)
- Mean Parent Symptom Survey Score at 10 Weeks(10 weeks after enrollment)
- Mean Parent Symptom Survey Score at 16 Weeks(16 weeks after enrollment)
- Mean Parent Symptom Survey Score at 18 Weeks(18 weeks after enrollment)
- Mean Systemic Adverse Events(Enrollment through 26 weeks)
- Distribution of Fellow Eye Visual Acuity at 26 Weeks(26 weeks after enrollment)
- Mean Fellow Eye Visual Acuity at 26 Weeks(26 weeks after enrollment)
- Distribution of Fellow Eye Visual Acuity Change From Baseline at 26 Weeks(26 weeks after enrollment)
- Mean Fellow Eye Visual Acuity Change From Baseline at 26 Weeks(26 weeks after enrollment)